Compositions and methods for augmentation or repair of intervertebral discs

Abstract

A method of augmenting and/or repairing an intervertebral disc by administering stem cell material into the disc. The stem cells may be undifferentiated cells, or they may be cells that have differentiated and have subsequently been dedifferentiated. The stem cells may be induced to express at least one characteristic of human intervertebral disc cells, such as fibroblast cells, chondrocyte cells, or notochordal cells, by exposing them to agents and/or environments calculated to induce the desired differentiation. In some embodiments, the stem cell material may be provided in conjunction with a collagen-based material, which may be a collagen-rich lattice or particles of collagen material. The stem cell material may be provided as a stem cell isolate, which may be substantially free of non-stem cell material. Other therapeutic agents may be administered with the stem cell material.

1 . A composition for treating an intervertebral disc, comprising stem cell material and a collagen-based material.  
     
     
         2 . A composition according to  claim 1  wherein said collagen-based material comprises a plurality of particles of a collagen-based material.  
     
     
         3 . A composition according to  claim 2  wherein said plurality of particles of a collagen-based material has a mean particle size of between 0.05 mm and 5.0 mm.  
     
     
         4 . A composition according to  claim 3  wherein said plurality of particles of a collagen-based material has a mean particle size of between 0.25 mm and 1.0 mm.  
     
     
         5 . A composition according to  claim 2  wherein said particles of a collagen-based material consists essentially of natural, collagen-rich tissue.  
     
     
         6 . A composition according to  claim 1  wherein said collagen-based material comprises a collagen-rich lattice.  
     
     
         7 . A composition according to  claim 6  wherein said stem cells are disposed in said collagen-rich lattice.  
     
     
         8 . A composition according to  claim 6  wherein said collagen-rich lattice material is harvested from the person into whom the composition is to be surgically added.  
     
     
         9 . A composition according to  claim 1  wherein said treating composition additionally includes a second agent selected from the group consisting of analgesics, antibiotics, radiocontrast materials, growth factors, crosslinking agents, polysaccharides, hormones, proteoglycans, and agents effective for treating degenerative disc disease.  
     
     
         10 . A composition according to  claim 9  wherein said second agent comprises one or more growth factors selected from the group consisting of transforming growth factor (TGF)-β, ascorbate-2-phosphate, bone morphogenetic proteins, fibroblast growth factors, platelet-derived growth factors, β-glycerophosphate, insulin, insulin-like growth factors, transferrin, and hydrocortisone.  
     
     
         11 . A composition according to  claim 9  wherein said second agent comprises one or more hormones selected from the group consisting of cytokines and morphogens.  
     
     
         12 . A composition according to  claim 1  wherein said stem cell material consists essentially of autologous stem cell material.  
     
     
         13 . A composition according to  claim 1  wherein said stem cell material consists essentially of human allogenic stem cell material.  
     
     
         14 . A composition according to  claim 1  wherein said stem cell material consists essentially of xenogenic stem cell material.  
     
     
         15 . A composition according to  claim 1  wherein said stem cell material consists essentially of stem cells that have never begun to differentiate.  
     
     
         16 . A composition according to  claim 1  wherein said stem cell material consists essentially of stem cells that have begun to differentiate but have been returned to an undifferentiated or substantially undifferentiated state.  
     
     
         17 . A composition according to  claim 1  wherein said stem cell material consists essentially of stem cells that have begun to differentiate, but have been returned to a partially-differentiated state.  
     
     
         18 . A composition according to  claim 1  wherein said stem cell material comprises stem cells that express or have been induced to express at least one characteristic of human intervertebral disc cells.  
     
     
         19 . A composition according to  claim 18  wherein said stem cell material has been induced to express at least one characteristic of human intervertebral disc cells by contacting the stem cell material with a member selected from the group consisting of transforming growth factor (TGF)-β, ascorbate-2-phosphate, bone morphogenetic proteins, fibroblast growth factors, platelet-derived growth factors, β-glycerophosphate, insulin, insulin-like growth factors, transferrin, and hydrocortisone.  
     
     
         20 . A composition according to  claim 18  wherein said stem cell material has been induced to express at least one characteristic of human intervertebral disc cells by contacting the stem cell material with mature cells of a desired phenotype.  
     
     
         21 . A composition according to  claim 1  wherein said stem cell material comprises stem cells that express or have been induced to express at least one characteristic of fibroblast cells.  
     
     
         22 . A composition according to  claim 1  wherein said stem cell material comprises stem cells that express or have been induced to express at least one characteristic of chondrocyte cells.  
     
     
         23 . A composition according to  claim 1  wherein said stem cell material comprises stem cells that express or have been induced to express at least one characteristic of notochordal cells.  
     
     
         24 . A composition according to  claim 1  wherein said stem cell material has been separated from non-stem cell material before being added to an intervertebral disc.  
     
     
         25 . A composition according to  claim 24  wherein said stem cell material is substantially free of non-stem cell material.  
     
     
         26 . A composition according to  claim 1  wherein said composition further includes a material effective for inducing stem cells to differentiate into intervertebral disc cells.  
     
     
         27 . A composition according to  claim 26  wherein said material effective for inducing stem cells to differentiate into intervertebral disc cells comprises a member selected from the group consisting of transforming growth factor (TGF)-β, ascorbate-2-phosphate, bone morphogenetic proteins, fibroblast growth factors, platelet-derived growth factors, β-glycerophosphate, insulin, insulin-like growth factors, transferrin, and hydrocortisone.  
     
     
         28 . A composition according to  claim 26  wherein said material effective for inducing stem cells to differentiate into intervertebral disc cells comprises mature cells of a desired phenotype.  
     
     
         29 . A method of treating an intervertebral disc, said method comprising surgically adding to an intervertebral disc a treating composition comprising stem cell material and a collagen-based material.  
     
     
         30 . An intervertebral disc that has been treated to repair damage done by degenerative disc disease, said disc comprising a disc annulus having contained therein a treating composition comprising stem cell material and a collagen-based material.